Epithelial wound healing is a major health concern, especially when the wound is located in the skin or in the cornea. The cornea is localized at the outer surface of the eye. It is a transparent organ, highly specialized and unique that is continually subjected to abrasive forces and occasional mechanical or chemical trauma because of its anatomical localization. A complete reepithelialization and the reorganization of a mature smooth stratified epithelium, as well as a structured stroma, is essential in restoring the imaging properties of the cornea. Damages to the cornea that can be due in part to slow wound healing can result in scarring or opacification that may lead to visual defects and even complete loss of vision in which case corneal transplant is required.
Corneal wounds account for 14% of the medical consultations and 8% of hospitalization for ocular problems in the ophthalmology units of North America. They can be superficial, with damage limited to the epithelium, or associated with a deeper involvement of the epithelial basement membrane and the stroma. Approximately 75% of all ocular damages result from mechanical or abrasive damages. Chemical burns accounts for 5 to 22% of the ocular wounds and between 30 to 80% of them result from damages caused by alkaline compounds (ammonia, sodium hydroxide, chemical glues). In addition, severe recurrent and persistent corneal wounds are often secondary to ocular diseases such as trauma, herpetic infections and autoimmune diseases of the cornea. Despite available treatments, many of these wounds persist for weeks and months or else recur frequently and can progress to corneal perforation with a risk of eye loss. Furthermore, one million laser vision corrective procedures are performed each year using refractive surgery in USA. Photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) are the most common methods used for the correction of myopia, hyperopia, and astigmatism. However, because of the higher risk of complications, such as haze and pain postoperatively, as well as more unpredictable refractive results after the correction of high ametropias with PRK, LASIK has become the most popular corneal refractive surgery in the world. The cellular and molecular regulatory phenomena associated with postoperative wound healing are likely to be involved in the adverse effects after these surgeries but their underlying mechanisms have not yet been clearly elucidated. In fact, variability in wound healing is often a major factor involved in cases with overcorrection, undercorrection, stromal opacity, and other complications that occur with these surgeries in the treatment of either myopia or hyperopia. Moreover, 1.82 million cataract surgeries are performed in the USA annually, making it the most common surgical procedure performed by healthcare providers. Although cataract surgery initially yields a good restoration of vision, secondary visual loss results following a wound-healing response within the remaining lens tissue; this leads to cells the deformation of the underlying collagenous posterior capsule and in the deposition of additional matrix components which cause light scatter and to a visual deterioration known as posterior capsule opacification (PCO). Complications, primarily due to wound healing difficulties, occur in 0.4% of cataract surgeries.
There is thus a need to provide methods and tools for determining the usefulness of putative therapeutic agent to improve and accelerate wound healing. There is also a need to provide compounds and combinations of compounds for improving and accelerating wound healing, especially in the skin and the cornea.